diet intervention and genetic study (digest-pilot)

Conditions: Cardiovascular Diseases; Inflammation; Dyslipidemias; Blood Pressure; Hyperglycemia

Summary: genetic factors contribute to risk factors for cardiovascular disease, such as blood lipids, blood pressure, obesity, diabetes, and may also influence dietary choices, physical activity, and responses to stress. the most robust genetic variant associated with myocardial infarction (mi) is the 9p21 variant, which may raise the risk of mi by up to 40% in those who carry 2 copies of the gene. the investigators recently found that among those who carry the 9p21 variant, the risk of mi may be "turned off" if individuals eat a diet high in fruits and vegetables. the investigators seek to determine how a "prudent" or "anti-inflammatory" diet interacts with the 9p21 risk allele to alter the risk of mi.

cardiovascular disease (cvd) is the leading cause of death globally. the majority of cvd is explained by conventional risk factors including cigarette smoking, abnormal lipids, high blood pressure, obesity, diabetes, and health behaviours including dietary intake, physical activity, and psychosocial stressors. genetic factors contribute to the development of these risk factors, and directly to cvd through other novel pathways. since the advent of high throughput chip-based genotyping, more than 30 genetic variants have been found to be associated with myocardial infarction. the most robust genetic variant which has been consistently associated with myocardial infarction and other forms of arterial disease is the 9p21 variant. this genetic variant located on chromosome 9 is common in the population, with 50% of people carrying one copy of the risk allele, and an additional 25% of the population carrying two copies of the risk allele. compared with those with no copies of the risk allele, the risk of myocardial infarction with one copy of the risk allele is 15-20% higher, and the increased risk among carriers of 2 risk alleles is 20-40%. to date the exact mechanism by which the 9p21 variant increases the risk of myocardial infarction is unknown, although some data suggests that other genes and pathways associated with cell proliferation and inflammation are involved. recently we made the observation that among carriers of the 9p21 variant, the risk of mi may be "turned off" if individuals consumed a diet high in fruits and vegetables. however the "mechanism" underlying this interaction is unknown. we seek to discover how a "prudent" (i.e. anti-inflammatory) diet interacts with the 9p21 risk allele(s) to alter the risk of myocardial infarction. we postulate that a "prudent" diet (i.e. a diet high in fruits, vegetables, whole grains, non-processed foods) in comparison to a "western" or "inflammatory diet" (eg, a typical north american diet high in saturated fats and processed foods) will differentially alter the gene expression (measured by rna) of the 9p21 locus, change the epigenetic marks in this region, and alter several inflammatory markers suspected to mediate the effect of 9p21 on cvd risk (eg, hs-crp, if-alpha21, ifn-γ , interleukin 1-alpha, interleukin 1-beta, and interleukin 6) among people with one or two copies of the risk allele compared to people without the risk allele. the proposed study offers an unique approach to studying dietary relationships with endpoints believed to be influenced by 9p21 gene variants. rather than testing nutritional supplements, our results will be generalizable to the setting of most dietary counseling practices, which aim to alter dietary patterns, not specific nutrients. this trial will help us to unravel the basis for gene-diet interactions and gain a greater understanding of how inflammation is linked to the development of atherosclerosis, cvd, and possibly some cancers.

Eligibility criteria:
inclusion criteria: * 18-80 years old * non-smokers * body-mass-index \<=30 kg/m\^2 * willing and able to cook, prepare, and eat provided study foods exclusion criteria: * aged below 18 years or above 80 years * current tobacco smoking * body mass index above 30 kg/m2 * unwillingness or inability to cook, prepare and eat provided study foods (e.g. for medical, philosophical, or religious reasons) * excessive use of alcohol (\>14 drinks/week in men; \>7 drinks/week in women) * significant morbidity that would interfere with participation or assessment, including : * cancer * hiv * chronic renal disease * renal failure * hepatitis/jaundice * liver disease * chronic obstructive pulmonary disease * inflammatory bowel disease (crohn's / colitis) * high blood or urine sugar/diabetes * high blood cholesterol or triglycerides * angina/heart attack/coronary artery disease * heart failure * other heart disease * angioplasty (balloon opening of an artery) or coronary bypass surgery * medications or nutritional supplements (including multivitamins) that could affect outcome measurements. excluded medications would include: * lipid/cholesterol lowering pills * insulin/oral hypoglycemic agents * medication for stroke * antibiotics * oral contraceptives * hormone replacement therapy * non-steroidal anti-inflammatory drugs * corticosteroids * unwillingness to stop nutritional supplements 1 week prior to and for duration of intervention * anticipated difficulties maintaining body weight (e.g. athletic training)

Keywords: diet dietary pattern gene gene expression epigenomics diet-gene interaction inflammation 9p21 fruits vegetables